Amorphous Drug–Polymer Salt with High Stability under Tropical Conditions and Fast Dissolution: The Challenging Case of Lumefantrine-PAA

Amorphous Drug-Polymer Salts

“…For example, indomethacin is more stable when formulated with Eudragit EPO, a salt former, than with HPMC, a neutral, non-salt-forming polymer [60]. Clofazimine and lumefantrine, both bases, are more stable when formulated with an acidic polymer than with a neutral polymer [62,64,65]. This confirms the importance of salt formation on the stability of amorphous drug-polymer formulations.…”

“…In the case of the amorphous LMF-PAA salt (50% drug loading), no crystallization was observed for at least 18 months, while the neutral dispersion in PVP or HPMCAS began to crystallize within weeks. Despite the higher stability, these amorphous drug-polymer salts showed fast dissolution and extended supersaturation in biorelevant media SGF and FaSSIF [64,65]. Their solid particles remained free flowing after storage at 40 • C/75% RH and showed improved tabletability.…”

“…We illustrate the formation of amorphous drug-polymer salts and their pharmaceutical benefits using the reaction of the acidic polymer poly(acrylic acid) (PAA) with two basic drugs, clofazimine (CFZ) [64] and lumefantrine (LMF) [65]. For both systems, a simple slurry method was used to produce the amorphous salt at a high drug loading (75% for CFZ-PAA and 50% for LMF-PAA).…”

“…Reproduced with permission from [64], American Chemical Society, 2021. (B) LMF-PAA salt (50% drug loading) [65]. No crystallization was observed after 18 months for LMF-PAA, while the neutral LMF−PVP and partially ionized LMF−HPMCAS dispersions at the same drug loading both crystallized.…”

“…No crystallization was observed after 18 months for LMF-PAA, while the neutral LMF−PVP and partially ionized LMF−HPMCAS dispersions at the same drug loading both crystallized. Reproduced with permission from [65], Elsevier, 2021.…”